Pyrrolo[3,4-c]pyrrole-1,4-dione, 2,5-dihydro-3,6-diphenyl-

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Basic data given: comparable to guidelines/standards

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1986

Report date:

1986

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

Deviations:

yes

Remarks:

only 1000 PCE counted

GLP compliance:

no

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Details on test material:

- Analytical purity: commercial grade
- Lot/batch No.: Op. 10002

Test animals

Species:

hamster, Chinese

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: CIBA-GEIGY Tierfarm, Sisseln
- Age at study initiation: female: 6-10 weeks, male: 4-9 weeks
- Weight at study initiation: female: 22-33 g, male: 27-35 g
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period:

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 - 23
- Humidity (%): 47 -50
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

- Vehicle(s)/solvent(s) used: 0.5% CMC (carboxymethyl cellulose)

Duration of treatment / exposure:

single treatment

Frequency of treatment:

single treatment

Post exposure period:

16, 24, 48 hours

Doses / concentrations

Remarks:

Doses / Concentrations:
5000 mg/kg
Basis:
actual ingested

No. of animals per sex per dose:

8

Control animals:

yes, concurrent vehicle

Positive control(s):

cyclophosphamide
- Route of administration: no data
- Doses / concentrations: 64 mg/kg at 20 mL/kg

Examinations

Tissues and cell types examined:

bone marrow

Details of tissue and slide preparation:

CRITERIA FOR DOSE SELECTION: In this experiment the dose of 5000 mg/kg was determined as the highest applicable in the mutagenicity assay.

DETAILS OF SLIDE PREPARATION: Small drops of the mixture were transferred on the end of a slide, spread out by pulling it behind a polished cover glass and the preparations were air-dried. Three hours later, the slides were stained in undiluted May-Gruenwald solution for 2 min then in May-Gruenwald solution/water 1/1 for 2 min and then in Giemsa's, 40% for 20 min. After being rinsed in methanol 55% for 5-8 sec and washed off twice in water,
they were left immersed in water for approx. 2 min. After rinsing with distilled water and air-drying, the slides were cleared in Xylene and mounted in Eukitt.

METHOD OF ANALYSIS: microscopically, 1000 polychromatic erythrocytes each were scored for the incidence of micronuclei per animal. The ratio of polychromatic to normochromatic erythrocytes was determined for each animal by counting a total of 1000 erythrocytes.

Statistics:

The significance ot difference was assessed by chi-square -test.

Results and discussion

Test results

Sex:

male/female

Genotoxicity:

negative

Toxicity:

no effects

Vehicle controls validity:

valid

Negative controls validity:

not examined

Positive controls validity:

valid

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative
It is concluded that under the conditions of this experiment, no evidence of mutagenic effects was obtained in Chinese hamsters treated with the test substance.